Chlorhexidine gluconate compositions, resin systems and article

ABSTRACT

Compositions containing chlorhexidine gluconate solubilized in hydrophobic vehicles are described. Resin systems containing such chlorhexidine gluconate compositions, including adhesives and articles incorporating such resin systems, including medical articles such as drapes are also described.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/627,548, filed Jun. 20, 2017, which is a continuation of U.S.application Ser. No. 15/185,165, filed Jun. 17, 2016, which iscontinuation of U.S. application Ser. No. 14/424,186, filed Feb. 26,2015, which is a national stage filing under 35 U.S.C. 371 ofPCT/US2013/056823, filed Aug. 27, 2013, which claims priority to U.S.Provisional Patent Application No. 61/694,088, filed Aug. 28, 2012, thedisclosure of which is incorporated by reference in its/their entiretyherein.

FIELD

The present disclosure relates to compositions containing chlorhexidinegluconate solubilized in hydrophobic vehicles, and resin systemscontaining such chlorhexidine gluconate compositions, includingadhesives. The present disclosure also relates to articles incorporatingsuch resin systems, including medical articles such as drapes.

SUMMARY

Briefly, in one aspect, the present disclosure provides a compositioncomprising chlorhexidine gluconate solubilized in a hydrophobic vehiclehaving a hydrophilic-lipophilic balance of no greater than 10 asdetermined using the HLB Method. In some embodiments, the hydrophobicvehicle comprises two proximate hydrogen-bonding groups, wherein atleast one of the hydrogen-bonding groups is a hydrogen donor. In someembodiments, the hydrophobic vehicle comprises an ester group, e.g., amonoacylglycerol. In some embodiments, the hydrophobic vehicle comprisesan ether group, e.g., dipropylene glycol and glyceryl monoalkyl ethers.In some embodiments, the hydrophobic vehicle comprises an alcohol havingproximate hydroxyl groups, e.g., 1,2-octane diol, 1,2-decane diol, andcombinations thereof.

In some embodiments, the composition comprises no greater than 1 part byweight hydrophilic vehicle per 1 part by weight chlorhexidine gluconate.In some embodiments, the composition comprises no greater than 0.1 partsby weight hydrophilic vehicle per 1 part by weight chlorhexidinegluconate. In some embodiments, the composition comprises no greaterthan 0.1 parts by weight water per 1 part by weight chlorhexidinegluconate.

In some embodiments, the composition further comprises a resin systemcomprising a polymer. In some embodiments, the resin system comprises ahydrophobic phase, wherein the hydrophobic vehicle plasticizes thehydrophobic phase. In some embodiments, the polymer comprises anacrylate polymer. In some embodiments, the polymer comprises a blockcopolymer polymer. In some embodiments, the resin system is a pressuresensitive adhesive.

In some embodiments, the composition comprises at least 0.2 wt. % CHG,based on the total weight of the composition. In some embodiments, thecomposition comprises at least 0.5 wt. % and no greater than 5.0 wt. %CHG, based on the total weight of the composition.

In another aspect, the present disclosure provides an article comprisinga substrate and a composition according to the present disclosure bondedto at least a portion of a surface of the substrate. In someembodiments, the composition is a pressure sensitive adhesive. In someembodiments, the substrate is selected from the group consisting offilms, nonwovens, wovens, and combinations thereof. In some embodiments,the substrate comprises at least one of polyalkylenes, polyesters,polyamides, and polyurethanes. In some embodiments, the article is amedical article, e.g., a drape or a dressing.

The above summary of the present disclosure is not intended to describeeach embodiment of the present invention. The details of one or moreembodiments of the invention are also set forth in the descriptionbelow. Other features, objects, and advantages of the invention will beapparent from the description and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The FIGURE illustrates an exemplary article incorporating a compositionaccording to some embodiments of the present disclosure.

DETAILED DESCRIPTION

Chlorhexidine digluconate, commonly referred to as “chlorhexidinegluconate” or “CHG,” is an antimicrobial useful in various applications.CHG is often provided as an aqueous solution, in part because CHG maydegrade in a non-aqueous composition. CHG has been provided innon-aqueous solutions by replacing water with a hydrophilic vehicle.Consistent with typical usage, as used herein, a “hydrophilic vehicle”is one having a hydrophile/lipophile balance (“HLB”) of greater than 10.For example, U.S. Pat. No. 6,458,341 (Rozzi et al., issued Oct. 1, 2002)describes non-aqueous solutions containing CHG and a solubilizingglycol, which is an exemplary hydrophilic vehicle.

Surprisingly, the present inventors have discovered that CHG can besolubilized in a wide variety of hydrophobic vehicles. Consistent withtypical usage, as used herein, a “hydrophobic vehicle” is one having ahydrophile/lipophile balance (“HLB”) of no greater than 10. Examples ofsuch hydrophobic vehicles include monoacylglycerides as described inInternational Publication No. WO2014/035971.

There are at least three distinct methods for preparing solutions of CHGin a non-aqueous vehicle. The first method involves mixing an aqueousCHG solution with a relatively high boiling vehicle, and then pulling avacuum on the mixture to remove the water (the “Vacuum Method’). Thesecond method involves lyophilizing CHG, and then dissolving the CHGinto the vehicle (the “Lyophilizing Method”). The third method involvesgenerating the CHG in situ by reacting gluconolactone, a limited amountof water, and chlorhexidine free base (the “In Situ Method). Each methodappears to give a similar final product, but each method has advantagesand disadvantages. For example, the lyophilization route does notrequire exposing the CHG to sustained heat, which helps preventdegradation. The liquid vacuum stripping route is easily scalable usingreadily available manufacturing equipment, e.g., kettles. The in situgeneration method does not require vacuum-equipped reactors.

All the methods may leave small amounts of water behind. Therefore, asused herein, “non-aqueous” refers to compositions that may contain smallamounts of water, e.g., less than 1 wt. %. In some embodiments, thecompositions contain less than 0.5 wt. %, e.g., less than 0.1 wt. % oreven less than 0.01 wt. % water. In some embodiments, the compositionscomprise no greater than 1 part by weight water per 1 part by weightCHG, no greater than 0.5 part by weight, no greater than 0.1 part byweight, or even no greater than 0.01 part by weight water per 1 part byweight CHG.

In some embodiments, the compositions contain little or no hydrophilicvehicle. As used herein, water is considered a separate componentindependent of any hydrophilic vehicles; therefore, the followingamounts are exclusive of any water which may be present in thecomposition. In some embodiments, the compositions comprise no greaterthan 2 parts by weight hydrophilic vehicle per 1 part by weight CHG,e.g., no greater than 1 part by weight, no greater than 0.5 part byweight, or even no greater than 0.1 part by weight hydrophilic vehicleper 1 part by weight CHG.

In the present disclosure, HLB values are calculated using the method ofGriffin (Griffin WC; J. Soc. of Cosmetic Chemists, pp. 249-256 (1954)).Thus, as used herein, the “HLB Method” involves a calculation based onthe following:HLB=(E+P)/5,where E is the weight percent of oxyethylene content and P is the weightpercent of polyhydric alcohol content (glycerol, sorbitol, etc.). Forthe compounds herein, glycerol segments with two hydroxyl groups,glycerol segments with one hydroxyl group, and hydroxyl-containingsegments of any additional polyhydric molecules were included in thedefinition of P.

As used in the present disclosure, hydrophilic vehicles have an HLBvalue as calculated using the HLB Method of greater than 10. In someembodiments, the hydrophilic vehicle has an HLB value of greater than11, e.g., greater than 12. Hydrophobic vehicles have an HLB value ascalculated using the HLB Method of no greater than 10. In someembodiments, the hydrophobic vehicle has an HLB value of no greater than9, e.g., no greater than 7.

Other methods of calculating HLB are available and may be required whendetermining the HLB value for compounds lacking both E and P groups, asdefined above. While the calculated value of HLB may vary depending onthe method used, the trends and relative hydrophobicity of materials areexpected to be similar.

In some embodiments, hydrophobic vehicles having proximate hydroxylgroups, e.g., vicinal hydroxyl groups, may be useful. As used herein,“proximate” groups refer to groups separated by no more than threecarbon atoms, as illustrated in Formulas I (hydroxyl groups separated bytwo carbon atoms) and II (hydroxyl groups separated by three carbonatoms). In some embodiments, the proximate groups may be vicinal, i.e.,separated by two carbon atoms, as illustrated in Formula I.

wherein RC═O is the acyl group. The depiction of 1-monoacylglycerides(Formula I) and 2-monoacylglycerides (Formula II) is merely intended toillustrate the meaning of proximate and vicinal groups and is notintended to, and does no limit the present invention to suchmonoacylglycerides.

In some embodiments, the compositions comprise at least 5% by weight CHGdissolved in the non-aqueous vehicle based on the combined weight of theCHG and the vehicle. In some embodiments, the compositions comprise atleast 10%, at least 15%, or even at least 20% by weight CHG dissolved inthe non-aqueous vehicle.

In some embodiments, compositions of the present disclosure comprisingCHG solubilized in a hydrophobic vehicle may be applied directly to asubstrate, e.g., sprayed or otherwise coated onto a porous or non-poroussubstrate. However, in addition to discovering that CHG could besolubilized in hydrophobic vehicles, the present inventors alsodiscovered that, when solubilized in a hydrophobic vehicle, CHG could beincorporated into a resin system such that the CHG remains available andeffective as an antimicrobial agent.

Depending on the hydrophobic vehicle, CHG may be incorporated into awide variety of resin systems. In some embodiments, one or morecomponents of the resin systems are themselves hydrophobic, and are thuscompatible with the hydrophobic vehicle. In some embodiments, the resinsystem may include both hydrophilic and hydrophobic components and/orphases, wherein the hydrophobic vehicle is compatible with at least thehydrophobic portion. In some embodiments, the hydrophobic vehicle isselected such that it plasticizes (i.e., is compatible with and lowersthe glass transition temperature of) the hydrophobic component or phase.In some embodiments, the hydrophobic vehicle is able to migrate throughthe resin system, carrying the solubilized CHG. For example, in someembodiments, the hydrophobic vehicle and solubilized CHG are able tomigrate to a surface of a layer of the resin system providing areplenishable supply of CHG to such a surface.

Generally, the resin system includes at least one polymer. In someembodiments, the resin system includes at least one hydrophobic polymeror phase. Suitable polymers include polyesters, polyester polyols,polyurethanes, polyalkylenes, acrylates, rubbers, block copolymers, andcombinations thereof. In some applications, the resin system may be anadhesive, e.g., a pressure sensitive adhesive (“PSA”).

In some embodiments, the PSA comprises an acrylic polymer or copolymercomprising the reaction product of a mixture comprising at least onealkyl (meth)acrylate monomer. As used herein, “(meth)acrylate” refers toan acrylate and/or methacrylate. For example, butyl (meth)acrylaterefers to butyl acrylate and/or butyl methacrylate. In some embodiments,the mixture may also include a crosslinking agent.

In some embodiments, the alkyl group of at least one alkyl(meth)acrylate contains 4 to 18 carbon atoms. In some embodiments, thisalkyl group contains at least 5 carbon atoms. In some embodiments, thisalkyl group contains no greater than 8 carbon atoms. In someembodiments, the alkyl group of the first alkyl (meth)acrylate has eightcarbon atoms, e.g., isooctyl (meth)acrylate and/or 2-ethylhexyl(meth)acrylate.

In some embodiments, the mixture may comprise one or more additionalmonomers including one or more additional alkyl(meth)acrylates. In someembodiments, the alkyl group of at least one of the additional alkyl(meth)acrylates contains no greater than 4 carbon atoms. In someembodiments, the alkyl group of at least one alkyl (meth)acrylate has 4carbon atoms, e.g., butyl (meth)acrylate. In some embodiments, the alkylgroup of at least one alkyl (meth)acrylate has 1-2 carbon atoms, e.g.,methyl acrylate and/or ethyl acrylate.

Examples of suitable polar monomers that may be copolymerized with thealkyl (meth)acrylate monomers include acidic monomers such as carboxylicacid monomers as well as various acrylamides. Particular examples ofpolar monomers include vinyl carboxylic acids such as acrylic acid,methacrylic acid, itaconic acid, maleic acid, fumaric acid, and2-hydroxyethyl acrylate or methacrylate. Other suitable polar monomersinclude N-vinyl pyrrolidone, N-vinyl caprolactam, acrylamide,methacrylamide, N-substituted and N,N-disubstituted acrylamides such asN-ethyl acrylamide, N-hydroxyethyl acrylamide, N,N-dimethyl acrylamide,N,N-diethyl acrylamide, and N-ethyl, N-dihydroxyethyl acrylamide,acrylonitrile, methacrylonitrile and maleic anhydride. Variouscombinations of such polar monomers can be employed.

Optionally, one or more monoethylenically unsaturated co-monomers may bepolymerized with the acrylate or methacrylate monomers. One group ofuseful co-monomers includes those having a homopolymer glass transitiontemperature greater than the glass transition temperature of the(meth)acrylate homopolymer. Examples of suitable co-monomers fallingwithin this group include acrylic acid, acrylamides, methacrylamides,substituted acrylamides (such as N,N-dimethyl acrylamide), itaconicacid, methacrylic acid, acrylonitrile, methacrylonitrile, vinyl acetate,N-vinyl pyrrolidone, isobornyl acrylate, cyano ethyl acrylate,N-vinylcaprolactam, maleic anhydride, hydroxyalkyl(meth)-acrylates,N,N-dimethyl aminoethyl (meth)acrylate, N,N-diethylacrylamide,beta-carboxyethyl acrylate, vinyl esters of neodecanoic, neononanoic,neopentanoic, 2-ethylhexanoic, or propionic acids (e.g., those availablefrom Union Carbide Corp. of Danbury, Conn., under the designationVYNATES), vinylidene chloride, styrene, vinyl toluene, and alkyl vinylethers.

A second group of monoethylenically unsaturated co-monomers that may bepolymerized with the acrylate or methacrylate monomers includes thosehaving a homopolymer glass transition temperature (Tg) less than theglass transition temperature of the (meth)acrylate homopolymer. Examplesof suitable co-monomers falling within this class includeethoxyethoxyethyl acrylate (Tg=−71 degrees Celsius) and amethoxypolyethylene glycol 400 acrylate (Tg=−65 degrees Celsius;available from Shin Nakamura Chemical Co., Ltd. Japan, under thedesignation “NK Ester AM-90G”).

In some embodiments, the PSA comprises a block copolymer. In someembodiments, the block copolymer is a styrenic block copolymer, i.e., ablock copolymer comprising at least one styrene hard segment, and atleast one elastomeric soft segment. Exemplary styrenic block copolymersinclude dimmers such as styrene-butadiene (SB) and styrene-isoprene(SI). Additional exemplary styrenic block copolymers includestyrene-isoprene-styrene (SIS), styrene-butadiene-styrene (SBS),styrene-ethylene/butadiene-styrene (SEBS), andstyrene-ethylene/propylene-styrene block copolymers. In someembodiments, radial and star block copolymers may be used. Commerciallyavailable styrenic block copolymers include those available under thetrade designation KRATON from Kraton Polymers LLC. including, e.g.,KRATON D SBS and SIS block copolymers; and KRATON G SEBS and SEPScopolymers. Additional commercially available di- and tri-block styrenicblock copolymers include those available under the trade designationsSEPTON and HYBAR from Kuraray Co. Ltd., those available under the tradedesignation FINAPRENE from Total Petrochemicals, and those availableunder the trade designation VECTOR from Dexco Polymers LP.

The resin systems of the present disclosure may contain any of a varietyof known additives including, e.g., crosslinkers, photoinitiators,curing agents, tackifiers, plasticizers, fillers, dyes, pigments, andthe like. As used herein, the terms tackifier and plasticizer are usedrelative to the material or phase into which they are incorporated.Thus, a “tackifier” is a material that is compatible with and raises theglass transition temperature of a material; while a “plasticizer” is amaterial that is compatible with and lowers the glass transitiontemperature of a material.

EXAMPLES

Objects and advantages of various embodiments of the present disclosureare further illustrated by the following examples, but the particularmaterials and amounts thereof recited in these examples, as well asother conditions and details, should not be construed to unduly limitthis invention. Unless otherwise indicated, all parts and percentagesare on a weight basis, all water is distilled water, and all molecularweights are weight average molecular weight.

Solubility Screening. Screening tests were conducted to determine thesolubility of CHG in a wide variety of vehicles. Tests were conductedusing the Vacuum Method and the Lyophilizing Method.

Vacuum Method. A 25 g sample of a CHG/water solution (20 wt. % solutionin water, obtained from Xttrium Laboratories Inc., Chicago, Ill.) wasadded to 45 g of the vehicle of interest in a 200 mL round bottom flask.The flask was put in a 60° C. oil bath and stirred with a magnetic stirbar. Vacuum (less than 3.3 kilopascal (25 Torr)) was pulled untilbubbling stopped and the weight had closely approached the theoreticalvalue of 50 grams—usually 30-90 minutes. In some cases, the vehicle wassomewhat volatile and the weight of the solution decreased significantlybelow 50 grams. In those cases, after nearly all the water was removed,additional vehicle was added to bring the final weight to 50 grams. Theresulting concentration of CHG and residual water were determined. Also,the final state of the solution was qualitatively evaluated to determineif the mixture was transparent and apparently homogenous, or clearlyinhomogeneous.

The results obtained using simple alcohols (i.e., compounds with onlyhydroxyl groups, carbon-carbon bonds, and carbon-hydrogen bonds) aresummarized in Tables 1a and 1b. The results obtained using compoundswith ester groups are summarized in Tables 2a and 2b. The resultsobtained using compounds with ether groups are summarized in Tables 3aand 3b.

TABLE 1a Simple alcohols as non-aqueous vehicles providing good CHGsolubility. CHG Water Compound wt. % wt. % Temperature Final StateGlycerol 10% 0.7% 23-50° C. Homogeneous 1,2-propanediol 10% 3.1% 23-50°C. Homogeneous 1,2-pentanediol 50% 3.3% 23-50° C. Homogeneous1,2-octanediol 10% 0.2% 23-50° C. Homogeneous 20% 0.3% 23-50° C.Homogeneous 1,2,6-trihydroxyhexane 10% 0.5% 23-50° C. Homogeneous1,3-propanediol 10% 0.7% 23-50° C. Homogeneous 1,4-butanediol 10% 1.7%23-50° C. Homogeneous 2-butene-1,4-diol 10% 1.2% 23-50° C. C Homogeneous1,3-butanediol 10% 2.2%   23° C. Inhomogeneous   50° C. Homogeneous  5%2.1% 23-50° C. Homogeneous 3-methyl-1,3-butanediol 10% N.T. 23-50° C.Inhomogeneous  5% N.T. 23-50° C. Inhomogeneous 2.5%  1.1%   23° C.Inhomogeneous   50° C. Homogeneous  1% 1.2%   23° C. Inhomogeneous   50°C. Homogeneous 1,3-cyclohexanediol 10% 1.6%   23° C. Inhomogeneous   50°C. Homogeneous  6% 4.8%   23° C. Inhomogeneous   50° C. Homogeneous2,3-butanediol 10% 1.2% 23-50° C. Homogeneous 50% 1,2-hexanediol 20%N.T. 23-50° C. Homogeneous 50% 1,2-pentanediol

TABLE 1b Simple alcohols as non-aqueous vehicles providing poor CHGsolubility. Compound CHG wt. % Temperature Final State 1,5-pentanediol10% 23-50° C. Inhomogeneous 1,8-octanediol 10% 23-50° C. Inhomogeneous2,5-hexanediol 10% 23-50° C. Inhomogeneous 2,3-dimethyl-2,3-butanediol10% 23-50° C. Inhomogeneous 1,4-cyclohexanediol 10% 23-50° C.Inhomogeneous 1-octanol 10% 23-50° C. Inhomogeneous

Several trends were identified from the data in Tables 1a and 1b.1,2-diols appear to impart CHG solubility. Other vicinal diols do notalways impart solubility, particularly when sterically hindered (e.g.2,3-dimethyl-2,3-butanediol). 1,3 diols appear to provide somesolubility, but may require elevated temperature. 1,4-butanediol, whichhas two primary alcohol groups, provides solubility. Other diolssimilarly separated by four carbon atoms but with secondary alcoholgroups do not provide good solubility (e.g., 2,5-hexanediol and1,4-cyclohexanediol). Even through 1,5-pentanediol and 1,8-octanediolhave two primary alcohol groups, the alcohol groups appear to be toowidely separated to impart good solubility.

TABLE 2a Vehicles with ester groups providing good CHG solubility. CHG.Water Compound wt. % wt. % Temperature Final State Medium Chain 20% 0.3%23-50° C. Homogeneous Monoglyceride Glyceryl monostearate 10% 0.2%   80°C. Homogeneous Glyceryl monocaprylate 20% ND   60° C. HomogeneousGlyceryl monolaurate 20% 0.7%   75° C. Homogeneous Glycerylmonoisostearate 20% ND   60° C. Homogeneous 16% 0.1% 23-60° C.Homogeneous 10% 0.7% 23-60° C. Homogeneous Diethyl-D-Tartrate 10% 0.5%23-50° C. Homogeneous Diethyl-L-Tartrate 10% 0.3% 23-50° C. HomogeneousDibutyl-L-Tartrate 10% 0.1% 23-50° C. Homogeneous Decaglyceryltristearate 10% 1.7% 23-50° C. Homogeneous Glyceryl monooleate 20% ND23-50° C. Homogeneous ND = not determined

TABLE 2b Vehicles with ester groups providing poor CHG solubility. CHGCompound wt. % Temperature Final State Dialkyl (C12 & C13) Tartrate 10%23-50° C. Inhomogeneous Diisopropyl-L-Tartrate 10% 23-50° C.Inhomogeneous Diisopropyl-D-Tartrate 10% 23-50° C. InhomogeneousDecaglyceryl pentaoleate 10% 23-50° C. Inhomogeneous Trigyceryldiisostearate 10% 23-50° C. Inhomogeneous PPG-5 Ceteth-20 10% 23-50° C.Inhomogeneous Isolaureth-10 10% 23-50° C. InhomogeneousPolyglycerol-2-Triisostearate 10% 23-50° C. Inhomogeneous Dimer Diol 5%23-50° C. Inhomogeneous Oxalic Acid Diethyl Ester 10% 23-50° C.Inhomogeneous

The trends observed for the esters in Tables 2a and 2b were similar tothe trends identified for the simple alcohols. Monoglycerides tend tohave a significant content of 1,2-diols and generally producehomogeneous solutions. Tartrates also have vicinal diols, but they donot have terminal hydroxyl groups. Tartrates with short alkyl chainsproduced homogeneous solutions, but when the alkyl groups become morebulky, the tartrates no longer produced homogeneity. With fatty acidesters of glycerol oligomers, it appears that the number of hydroxylgroups needs to be large compared to the number of non-polar fatty acidgroups to achieve homogeneity.

TABLE 3a Vehicles with ether groups providing good CHG solubility. CHG.Water Compound wt. % wt. % Temperature Final State Triethylene glycol10% 0.2% 23-50° C. Homogeneous Tetraethylene glycol 10% 0.1% 23-50° C.Homogeneous Triethyleneglycol 10% 2.4% 23-50° C. Homogeneous monomethylether Diethyleneglycol 10% 2.2% 23-50° C. Homogeneous monomethyl etherDiethyleneglycol 10% ND 23-50° C. Inhomogeneous monoethyl ether  5% ND23-50° C. Inhomogeneous 2.5%  1.4% 23-50° C. Homogeneous Dipropyleneglycol 10% 0.5%   23° C. Inhomogeneous   50° C. Homogeneous  5% 1.5%23-50° C. Homogeneous Sorbeth-6 10% ND 23-50° C. Homogeneous 1,3- 10%2.1% 23-50° C. Homogeneous dihydroxyacetone dimer Ethylhexyl glycerin10% 0.1% 23-50° C. Homogeneous 20% 1.0% 23-50° C. Homogeneous

TABLE 3b Vehicles with ether groups providing poor CHG solubility. CHGCompound wt. % Temperature Final State Diethyleneglycol Monobutyl Ether10% 23-50° C. Inhomogeneous Polyethyleneglycol Dimethyl Ether 10% 23-50°C. Inhomogeneous Diethyleneglycol Dimethyl Ether 10% 23-50° C.Inhomogeneous Tripropylene glycol 10% 23-50° C. InhomogeneousDecaglyceryl pentaoleate 10% 23-50° C. Inhomogeneous Trigyceryldiisostearate 10% 23-50° C. Inhomogeneous PPG-5 Ceteth-20 10% 23-50° C.Inhomogeneous

The trends observed with the ethers are somewhat different than thoseobserved for the simple alcohols and ester-containing vehicles.Oligoethylene glycols with hydroxyl groups at each end of the chaintended to give homogenous solutions. As one of the hydroxyl groups isreplaced with an ether the appearance of homogeneity seems to depend onthe size of that ether group. On the other hand, propylene glycololigomers are much less likely to give homogeneous solutions, and eventhe most favorable case—dipropylene glycol—only produced homogeneity atelevated temperatures or relatively low concentrations.

Based on the foregoing, the present inventors discovered that CHG can besolubilized in a wide variety of hydrophobic vehicles, as summarized inTable 4. HLB values calculated according to the HLB Method are included.Relying on these test methods and the trends observed in the results,one of ordinary skill in the art could readily identify additional suchhydrophobic vehicles.

TABLE 4 Summary of hydrophobic vehicles providing good solubility forCHG. Class Vehicle HLB alcohol 1,2-octanediol 8.4 ester Decaglyceryltristearate 9.7 ester Glyceryl monocaprylate 8.4 ester Glycerylmonolaurate 6.6 ester Glyceryl monostearate 5.1 ester Glycerylmonoisostearate 5.1 ester Glyceryl monooleate 5.1 ether Dipropyleneglycol 9.1 ether Ethylhexyl glycerin 8.9

The Lyophilization Method. Lyophilized CHG was prepared by freeze-dryingthe aqueous CHG solution (20 wt. % solution in water, obtained fromXttrium Laboratories Inc., Chicago, Ill.).

For lower viscosity vehicles, a 5 ml sample of the non-aqueous vehicleof interest was measured into a glass vial. For higher viscosityvehicles that were difficult to transfer by volume, a 5 gm sample wasweighed into the vial. Next, 0.01 g of lyophilized CHG was added to thevial. The sample was capped and mixed by shaking for 30 seconds. Thesample was immediately observed and then observed again after 2 minutesand again after 24 hours. After 24 hours, the sample was placed in a 50°C. oven for 2 hours and then removed and immediately observed. Thesesamples were allowed to cool to room temperature and a final observationwas made. The results are summarized in Table 5.

TABLE 5 Vehicles evaluated using 0.2 wt. % lyophilized CHG obtained byfreeze-drying. Apparent solubility 2 >24 2 hours after Vehicle immediateminutes hours 50° C. cooling Acetytriethyl citrate no no partial solublepartial Diisostearyl dimerate no no no soluble no Dipropylene glycol nono soluble soluble soluble Glycerol triisostearate no no partial partialpartial Isostearate caprylic/ partial partial soluble soluble solublecapric glycerides Glycereth-18 no no soluble soluble solubleEthylhexanoate Isolaureth-10 no no partial soluble solublePPG-5-ceteth-20 no no partial soluble soluble Octyldodeceth-10 nopartial partial partial partial Oleth-2 no no no partial partialIsostearyl isostearate no no no partial partial PEG-20 glyceryl nopartial partial partial partial Triisostearate Pentaerythritol partialpartial partial partial partial tetraisostearate Polyglycerol-3 no nosoluble soluble partial Diisostearate Propylene glycol no no partialpartial partial Dicaprylate/caprate

Generally, the results were similar to those observed using the VacuumMethod. Specifically, polar functional groups, particular when closetogether, tended to provide CHG solubility. For some vehicles, CHG wassoluble at the low concentrations used with the Lyophilization Method,but at least partially insoluble at the higher concentrations used inthe Vacuum Method.

Generally, CHG is added to a composition such that its finalconcentration is at least 0.2 wt. %, in some embodiments at least 0.5wt. %, in some embodiments at least 1.0 wt. %, in other embodiments atleast 2.0 wt. %, in yet other implementations at least 5.0 wt. %, and insome cases exceeding 10 wt. %, based on the total weight of thecomposition. Generally, the CHG concentration is no greater than 25 wt.%, more preferably no greater than 20 wt. %, and most preferably nogreater than 15 wt. %, based on the total weight of the composition. Atypical range for CHG concentration to enhance active kill is at least0.5 wt. % and no greater than 5.0 wt. %, based on the total weight ofthe composition.

As illustrated in the following examples, compositions comprising CHGsolubilized in such vehicles can be incorporated into a wide variety ofresin systems and in the preparation of a wide variety of articles.Materials used in the preparation of the examples are summarized inTable 6a and 6b.

TABLE 6a Summary of materials used in the preparation of the examples.Name Description Trade Name and Source CHG chlorhexidine gluconate,Xttrium Laboratories, Inc., 20 wt. % solution in water Chicago, IllinoisMRSA Methicillin Resistant American Type Culture CollectionStapyhlococcus Aureus (ATCC #33592), Manassas, Virginia Film-1 polyesterelastomer film E. I. du Pont de Nemours & Co., (HYTREL 4056 resin)Wilmington, Delaware Resin systems Res-1 amorphous polyester polyolPRIPLAST 3193, Croda Inc., Edison, NJ Res-2 amorphous polyester polyolPRIPLAST 3197; Croda Inc. Res-3 amorphous polyester polyol PRIPLAST 1838(MW 2000); Croda Inc. Res-4 amorphous polyester polyol PRIPLAST 3196 (MW3000); Croda Inc. PSA-1 isooctyl acrylate/ 3M Company,N-vinylpyrrolidone St. Paul, Minnesota PSA-2 isooctylacrylate/acrylamide 3M Company PSA-3 isooctyl acrylate/vinyl 3M Companyacetate/acrylamide PSA-4 tackified KRATON block 3M Company copolymeradhesive

TABLE 6b Summary of vehicles used in the preparation of the examples.HLB Description Trade Name and Source Hydrophobic Vehicles 8.9ethylhexyl glycerin SENSIVA SC 50 Schulke & Mayr, Norderstedt, Germany8.4 glycerol monocaprylate Abitec Corp, Janesville, Wisconsin 7.5sorbitan isostearate Croda Inc. 7.2 decaglycerol pentaoloeate BarnetProducts Corp, Englewood Cliffs, New Jersey 7.0 1,2-decanediol Symrise,Teterboro, NJ 6.8* medium chain monoglyceride MCM, Abitec Corp,Janesville, (MCM-1) Wisconsin 6.8 medium chain monoglyceride MCM-NF,Abitec Corp. (MCM-2) 5.1 glycerol monoisostearate (GMIS-1) JEEN GMIS,Jeen Corp., Fairfield, NJ 5.1 glycerol monoisostearate (GMIS-2) CRODAGMIS Croda Iberica, Barcelona, Spain 5.1 glycerol monoisostearate(GMIS-3) LUBRIZOL GMIS Lubrizol Adv. Mtls., Cleveland, Ohio 5.1 glycerolmonooleate Gattefosse SAS, St. Priest, France 3.3 sorbitan trioleateAldrich Chemicals, Milwaukee, WI Hydrophilic Vehicles 11.71,2-pentanediol Symrise, Teterboro, NJ 15.9** 1,2,3-triacetoxypropane(triacetin) Aldrich Chemicals, Milwaukee, WI 16.0 1,2-propanediolAldrich Chemicals, Milwaukee, WI 20.0 glycerol EM Science, Gibbstown,New jersey *Estimate based on available compositional information**Estimate based on literature values and modified calculationsincluding C═O and glycerol groups as hydrophilic components.

CHG solutions. The solutions containing CHG were either a 20 wt. %aqueous solution of CHG or a 10-20% w/w solution of CHG in a non-aqueousvehicle. The non-aqueous solutions were prepared by freeze drying theaqueous CHG solution to produce lyophilized CHG. Finely divided,lyophilized CHG was then solubilized in a non-aqueous vehicle at roomtemperature with continuous stirring for eight hours

Adhesive Preparation Procedure. Adhesive compositions were prepared byblending together a solvent-based pressure sensitive adhesive and asolution of CHG in a non-aqueous vehicle through simple manualagitation.

Adhesive Coating Procedure. Adhesive compositions were coated ashand-spreads by applying a uniform layer of the adhesive on the releasesurface of a suitable release liner using a knife-edge coater. The wetadhesive thickness ranged from 50 to 510 microns (2-20 mils). The coatedadhesives were dried in a solvent oven for 1-10 minutes at temperaturesbetween 65 and 93° C. (150 and 200° F.).

Adhesive Lamination Procedure. The dried adhesives were used to prepareadhesive articles samples by laminating the dried adhesive to a suitablebacking using nip rollers at room temperature.

CHG Surface Availability Analysis. In some embodiments, a discreteamount of CHG should be available at the surface of the adhesive.Surface availability was determined by exposing the surface of the driedadhesive to water in a resting state, according to the following method.A sample of an adhesive article sufficient to cover a circular area of660 square millimeters was cut from a larger section of an adhesivearticle prepared as described above. Water (4.0 mL) was pipetted into aglass cup. The release liner was removed exposing a surface of the driedadhesive, and the sample was applied evenly to the top of the glass cupand pressed tight to seal the adhesive to the glass cup so it did notleak when inverted. The sample was then inverted. After the desired testtime had elapsed, the sample was reverted and immediately opened. Analiquot of the water was transferred to an LC vial for analysis. Sampleswere analyzed by reversed-phase HPLC using absorbance detection on anAgilent 1200 HPLC system consisting of a quaternary gradient pump,autosampler, heated column compartment and variable wavelength detector.5.0 mcL portions of sample solutions were injected onto a MACMODAnalytical Inc. 150×3 mm ACE 3 micometer C18 column. The column wasequilibrated with 80/20 v/v water/methanol containing 40 mM pH 3.7ammonium formate buffer at 0.50 mL/min and 40° C. Following injectionthe samples were eluted with a 30 min linear gradient to 20/80 v/vwater/methanol containing 40 mM pH 3.7 ammonium formate buffer. Thiseluent composition was held isocratically for 5 minutes beforere-equilibration in the starting eluent. Absorbance detection of the254±2 nm signal was utilized to quantify sample concentration ofchlorhexidine gluconate against standard solutions containingchlorhexidine acetate (“CHA”). A molar fraction of 1.435 was applied tothe quantitation to account for the molar ratio of CHG/CHA (898/626).

Direct Time Kill Analysis. Specimens of several coated adhesives weresubjected to antimicrobial performance testing according to thefollowing 5-30 minute time kill study. A suspension of methicillinresistant Staphylococcus aureus (MRSA, ATCC #33592) was prepared at aconcentration of 1×10⁸ CFU (colony forming units) per milliliter (mL) inphosphate buffered water (pbw) using a 0.5 McFarland EquivalenceTurbidity Standard. Using an Eppendorf pipette, 50 micro liters (μL) ofthis suspension was transferred as 15-16 separate droplets to theadhesive surface of a 2.5 cm diameter section of an adhesive film. Theseinoculated specimens were then incubated at room temperature (23+/−2°C.) for 5-30 minutes. After incubation, the specimens were placed in 20mL of neutralizing buffer and sonicated for one minute followed byvortexing for two minutes. Portions of the resulting solution wereserially diluted with pbw. The neat solution and dilutions were eachplated to 3M PETRIFILM aerobic count plates (3M Company) and incubatedfor at least 24 hours. The 3M PETRIFILM plates were then counted using a3M PETRIFILM plate reader (model 6499, 3M Company).

Example Set A

These examples show the antimicrobial efficacy of several CHG containingresin systems using the Direct Time Kill Analysis. Generally, the CHGwas solubilized in a hydrophobic vehicle. The hydrophobic vehicle wascompatible with and plasticized (i.e., reduced the Tg of) thehydrophobic phase of the base adhesive. The formulations were preparedby premixing the hydrophobic vehicle(s) with aqueous CHG, diluting withheptane, and mixing the solution with the solvent-based adhesive. Theresulting mixture was coated on a silicone release liner at 4.6mg/square centimeter, dried and laminated to Film-1. When the waterphase evaporated from the adhesive, it left behind CHG solubilized inthe hydrophobic vehicle, which was dispersed in the adhesive. Theadhesives were tested for antimicrobial activity using the Direct TimeKill Analysis with an incubation period of 5 minutes. The formulationsand log reduction results are shown in Table 7. All the examplescontaining CHG solubilized in a vehicle that plasticized the adhesiveshowed good bacteriocidal activity at five minutes relative to thesample without CHG, i.e., Comparative Example (CE-1).

TABLE 7 Sample compositions (wt. %) prepared with PSA 3, and logreductions. 1,2- Ethylhexyl Decaglycerol Glyceryl Decanediol glycerinpentaoleate monocaprylate (HLB = (HLB = Ex. PSA (HLB = 7.2) (HLB = 8.4)7.0) 8.9) CHG Log Red. CE-1 50 30 10 10 — 0 0 A1 50 28 20 — — 2 3.5 A250 28 10 10 — 2 3.3 A3 50 28 — — 20 2 3.6

Example Set B

These examples showed the effect of using hydrophilic non-aqueousvehicles that did not plasticize the adhesive as compared to thehydrophobic non-aqueous vehicles that did plasticize the adhesive. Theformulations were prepared by premixing the vehicle or vehicle blendswith aqueous CHG, diluting with heptane, and mixing the solution with asolvent-based adhesive. All samples contained 2 wt. % CHG and used PSA-2except Comparative Example CE-2, which used PSA-1. The resulting mixturewas coated on a silicone release liner at 4.6 mg/square centimeter,dried and laminated to Film-1. The adhesives were tested forantimicrobial activity according to the Direct Kill Time Analysis, withan incubation period of 5 minutes. The compositions and log reductionresults are shown in Table 8.

TABLE 8 Compositions (wt. %) and log reductions for samples containing 2wt. % CHG. 1,2- 1,2- 1,2- Glyceryl Log EX. PSA Res-1 Res-2 pentanediolpropanediol decanediol monocaprylate GMIS-2 Red. HLB 11.7 16.0 7.0 8.45.1 CE-2 55 — — 43 — — — — 0.4 CE-3 50 24 — — 24 — — — 0.3 B1 55 — 20.5— — 11.25 11.25 — 5.7 B2 55 — — — — 11.25 11.25 20.5 6.1 B3 60 — — — —10 10 18 6.2

Both pentanediol (CE-2) and propanediol (CE-3) are hydrophilic vehicles(HLB>10) that effectively solubilize the CHG but do not plasticize thehydrophobic isooctyl acrylate rich domains of the adhesive. Theantimicrobial activity of these compositions is very poor. In contrast,the use of hydrophobic vehicles such as 1,2-decanediol, glycerylmonocaprylate, and glyceryl isostearate (HLB<10) provided both goodsolubility of CHG and good compatibility with the hydrophobic domainsresulting in very high log reductions.

Data Set C. These examples demonstrate the importance of using at leastone vehicle capable of dissolving CHG as a plasticizer in the adhesivesystem in order to obtain surface activity. The formulations wereprepared by premixing the vehicle or vehicle blends with aqueous CHG,diluting with heptane, and mixing the solution with a solvent basedadhesive. The mixtures was coated on a silicone release liner at 4.6mg/square centimeter, dried and laminated to Film 1. The adhesives weretested for antimicrobial activity using the Direct Time Kill Analysiswith an incubation period of 15 minutes.

TABLE 9 Compositions (wt. %) and log reduction. Sorbitan Sorbitan LogEX. PSA 3 trioleate GMIS-1 GMIS-2 isostearate MCM CHG Reduction CE-4 55— — 22.5 22.5 — 0 0.8 CE-5 55 21.5 21.5 — — — 2 0.6 CE-6 55 — 43 — — — 21.2 C1 55 — — 21.5 21.5 — 2 5.5 C2 55 — — — 21.5 21.5 2 5.5 C3 65 — — —— 33 2 5.5

Dissolution experiments using lyophilized CHG showed that while GMIS-2was a good solvent for CHG, the solubility of CHG in GMIS-1 and sorbitantrioleate was limited. Analytical tests showed that GMIS-2 contained ahigher weight fraction of monoesterified compounds than GMIS-1, which isbelieved to contribute to the improvement in CHG solubility.Accordingly, the two adhesive samples containing GMIS-1 (CE-6) or GMISand sorbitan trioleate (CE-5) showed very little efficacy with resultscomparable to CE-4, which did not contain CHG. The three remainingformulations, each of which used a hydrophobic vehicle(s) thatsolubilized CHG, showed almost complete bacterial kill.

Once incorporated into a resin system, compositions comprising CHGsolubilized in a hydrophobic vehicle may be suitable for a wide varietyof applications. For example, such compositions can be incorporated intoa wide variety of articles including medical articles. Exemplary medicalarticles include drapes (e.g., surgical drapes and incise drapes), anddressings (e.g., wound dressings and I.V. dressings).

On exemplary article is illustrated in the FIGURE. Article 100 includessubstrate 110 and CHG-containing composition 120 adhered to at least aportion of at least one surface of the substrate. In some embodiments,it is desirable to have a replenishable supply of CHG available atcomposition surface 125 to provide the desired persistent antimicrobialaffect.

Generally, any known substrate may be used including, e.g., films,nonwovens, wovens, and combinations thereof. Substrates can be preparedfrom a wide variety of materials including, e.g., at least one ofpolyalkylenes, polyesters, polyamides, and polyurethanes. In someembodiments, composition 120 is directly bonded to substrate 110, asshown in the FIGURE. In some embodiments, the composition may beindirectly bonded to the substrate through one or more intermediatelayers, including e.g., tie layers used to promote adhesion. Thefollowing examples illustrate exemplary embodiments of articles of thepresent disclosure.

Data Set D. These examples showed the effect of vehicle loading onsurface availability and antimicrobial activity. The formulations wereprepared by premixing MCM-1 with aqueous CHG, diluting with heptane, andmixing the solution with a solvent-based adhesive (PSA-1). MCM-1 is ahydrophobic vehicle that plasticized the hydrophobic phase of the PSA-1adhesive. The mixture was coated on a silicone release liner at 4.6mg/square centimeter, dried and laminated to Film-1. Surface extractionof the finished adhesive was performed according to the CHG SurfaceAvailability Analysis to quantify the CHG released in quiescent waterafter 30 minutes. As the plasticizer fraction in the adhesive increased,there was a concomitant increase in the amount of CHG released per unittime. The effect of the difference in release can also be seen in thedirect time kill data. The compositions, surface availability (“SA”)reported as micrograms per square centimeter, and direct kill timeresults are summarized in Table 10.

TABLE 10 Compositions (wt. %), SA (micrograms/square centimeter) and logreductions. Log Reduction 5 EX. PSA 1 MCM-1 CHG SA min. 10 min. 15 min.20 min. D1 75 23 2 4.2 4.4 5.3 5.7 5.7 D2 50 48 2 7.5 5.5 5.7 5.7 5.7

Drape Adhesion Analysis. Pigskin was used as a proxy for human skin togauge the adhesive performance of the adhesive article samples. The testmethod described in Grove, G. L. et al.; The Journal of Bone & JointSurgery; Vol. 94A, No. 13; 2012; pp. 1187-1192, “Comparison of twopreoperative skin antiseptic preparations and resultant surgical incisedrape adhesion to skin in healthy volunteers” was followed with thefollowing exceptions. Briefly, freshly euthanized pigs were clipped andshaved prior to prepping the skin with isopropyl alcohol. Each preppedarea was allowed to dry for about 5 minutes and not more than 6 minutes.Strips cut 1.3 cm by 7.6 cm (0.5 in by 3 in) were applied in duplicateover the prepped area so that the long axis of the drape strip wasorientated perpendicular to the pig's spine. To assure even applicationof the drape samples to the skin, a 2 kg (4.5 lb) roller was rolled overthe drape samples once back and forth, using no additional pressure,immediately after the drape samples have been placed onto the test site.After the drape samples had been pressed in place with the roller, theywere allowed to build adhesion for up to 5 minutes+/−30 seconds beforeany saline challenges were applied.

A 10 cm by 10 cm (4 in by 4 in) gauze that had been soaked in a 0.9%saline solution was placed over the drape sample immediately after thespecified adhesion build time. Extra saline was added to the gauze at 10minutes+/−2 minutes intervals during the challenge period to keep itsaturated. The gauze was removed after 30 minutes+/−30 seconds.Immediately after removing the gauze from each sample, the drape samplewas mechanically removed using a peel tester. The pull rate was 30.5 cmper minute (12 inches/min) at an angle of approximately 90 degrees tothe skin. Data acquisition software was used to record the peel adhesionforce.

Data Set E. These examples demonstrate the ability of adhesive articlesprepared from adhesives plasticized with a hydrophobic vehiclecontaining CHG to adhere well to euthanized pigs under simulatedirrigation. The control sample used was an antimicrobial incise drapemarketed under the brand name IOBAN from 3M Company, St. Paul, Minn.Three CHG-containing, solvent-based adhesive formulations were preparedby combining 25 parts by weight PSA-3 (provided as 100 parts by weightof a solution containing 25 wt. % PSA-3 dissolved in ethylacetate/methanol) with 25 parts by weight hydrophobic vehicle(s), 5parts by weight of a 20 wt. % aqueous solution of CHG, and 75 parts byweight ethanol. Each adhesive was coated onto a silicone liner at 4.6mg/square centimeter, dried, and laminated to Film-1 to prepare adhesivearticles. The resulting compositions of the dried adhesives aresummarized in Table 11. The results of the adhesion to pigskin under wetchallenge are also summarized in Table 11. The reported values are theaverage and standard deviations are based on six replicates.

TABLE 11 Compositions (wt. %) and adhesion results in grams per 1.2 cm.Vehicles Adhesion Ex. PSA-3 Res-2 V1 V2 V3 CHG Average Std. Dev. E1 49 —29.4 9.8 9.8 2 120 30 E2 49 29.5 — 9.8 9.8 2 110 20 E3 54 — 29.4 9.8 9.82 70 30 CE-7 Ioban (TM) drape (3M Co.) 110 20 V1 = decaglycerolpentaoleate (HLB = 7.2) V2 = glyceryl monocaprylate (HLB = 8.4) V3 =1,2-decanediol (HLB = 7.0)

In some embodiments, the ability to sterilize the final CHG-containingadhesive article, with, e.g., ethylene oxide (EO) or gamma irradiation,is a highly desired performance characteristic. For example, in someembodiments, it may be desirable to include the adhesive article in kitsand be sterilized by EO as a part of those kits. The effect of EOsterilization on the adhesive formulation of Example E1 was evaluated.The sample was subject to a standard EO cycle and tested forantimicrobial activity using the Direct Time Kill Analysis at 5 minuteand 30 minute incubation periods. No bacteria were detected afterenumeration at both time periods, indicating complete kill. Thesterilization cycle has no deleterious effect on the CHG activity inadhesive article.

It is known that aqueous CHG is unstable to gamma irradiation. In orderto assess the effects of gamma radiation of CHG dissolved in non-aqueoussolvents, two samples were prepared with a composition of 65% w/w PSA-3,33% w/w MCM-1 and 2% w/w CHG. Example F1 was prepared without water withthe CHG source being a 20% w/w solution of lyophilized CHG predissolvedin MCM-1. In Example F2, the CHG source was a 20% w/w solution in water,with the water removed during drying. The samples were exposed to twodifferent doses of gamma radiation: 25 and 45 kGy. These irradiatedsamples were then tested using the Direct Time Kill Analysis after 5minutes of incubation. The results are shown in Table 12. Surprisingly,there was no negative effect of gamma irradiation observed on the CHGsolubilized in non-aqueous vehicles. Furthermore, the activities werethe same whether the CHG was pre-dissolved in the vehicle or dissolvedin situ through the evaporation of water.

TABLE 12 Log reduction as a function of gamma radiation. Gamma Dose Ex.None 20 kGy 45 kGy F1 5.7 5.5 5.7 F2 5.7 5.7 5.7

The effect of accelerated aging on the activity of CHG in the adhesiveof an adhesive article was evaluated. Adhesive articles were preparedcontaining 58% w/w PSA-2, 20% w/w triacetin, 20% w/w glycerylmonocaprylate, and 2% w/w CHG. These samples were aged at 66° C. (150°F.) for six weeks. This aggressive aging schedule corresponds to twoyears aging at room temperature using the Van't Hoff rule. The sampleswere removed from the aging oven at the end of six weeks and tested forantimicrobial activity using the Direct Time Kill Analysis after 5 and30 minutes of incubation. The aged samples showed a 0.2 log reductionafter 5 minutes and a 3.1 log reduction after 30 minutes of incubation.Thus, there was considerable antimicrobial activity even after thisextreme thermal treatment.

Data Set H. In some embodiments, a high Moisture Vapor Transmission Rate(MVTR) value may be desired, e.g., it may be desirable for CHG incisedrape materials to prevent accumulation of moisture and skin macerationunder the incise drape when it is applied for very long surgeries. Boththe permeability properties of the backing and the adhesive (type andcoat weight) impact MVTR.

To evaluate the MVTR of various drape examples, the following stockformulations were prepared. Formulation HA contained 49 wt. % PSA 2,22.5% glycerol monoisostearate (GMIS-2), 22.5% sorbitan isostearate, 5%glycerol, and 1% CHG. Formulation HB was identical except ethylhexylglycerin was used instead of the sorbitan isostearate. Drape examplesH1-H4 were prepared by laminating formulations HA or HB to a HYTREL filmbacking. Tie layers were used in Examples H2-H4 to aide in bonding theformulations to the HYTREL backing.

Moisture Vapor Transmission Rate (MVTR) Analysis. The MVTR wasdetermined using a variation of ASTM method E96-80. The film was placedadhesive side down over the opening of a standard glass vessel halffilled with deionized water. The MVTR was determined by first allowingthe sample 24 hours to equilibrate to the test conditions of 39 degreeC. and 20% ambient relative humidity and then measuring the weight lossof water occurring over the following 24 hours.

TABLE 13 Compositions and moisture vapor transmission rates (g/sqmeter/24 hours). EX. Drape Composition Description MVTR Std Dev CE-8HYTREL film only 1380 17 CE-9 IOBAN Surgical Drape 470 13 FormulationTie-layer H1 HA (4.6 mg/cm²) None 680 13 H2 HA (2.5 mg/cm²) PSA 2 (2.5mg/cm²) 410 13 H3 HB (3.8 mg/cm²) PSA 4 (1.26 mg/cm²) 290 7 H4 HB (2.5mg/cm²) PSA 4 (2.5 mg/cm²) 140 10

Data Set J. The primary function of an incise drape is to adhere well tothe skin, providing a physical barrier that prevents the transfer ofresident skin microorganisms into the surgical wound. This performancerequirement is challenging for a skin-friendly adhesive to meet. Afterthe adhesive film is applied to the patient, an incision is made with ascalpel. The deeper layers of tissue are then cut away using acombination of surgical instruments to gain access to the area ofinterest.

Adhesive performance of an incise drape must be evaluated using acombination of methods to assure adequate performance in the operatingroom. The drape must remain adhered to the skin all the way up to theedge throughout all of the manipulation performed in a typical surgery.In a typical surgery, a surgeon and nurse might insert and remove theirhands, surgical instruments, implants, bones, and tissue multiple timesover the course of several hours. The adhesive drape is also exposed tolarge volumes of irrigation fluid, saline, blood, and other bodilyfluids, and must maintain its adhesion. After holding up to thechallenges of a surgical procedure, the adhesive drape must still berelatively easy to remove from the skin, not causing significant pain orskin damage near the incision.

Peel testing on human or porcine skin is one accepted way to assess theperformance of an adhesive tape or film on skin. Briefly, strips ofadhesive coated backing are applied to the subject, allowed to adherefor a set dwell time, and removed using a device that measures theaverage force of removal at 90 degrees. The higher the force of removal(or peel value), the more difficult the adhesive is to remove from theskin surface. The peel value can give an indication of the ability ofthe adhesive construction to remain adhered to the skin. For an incisedrape, a desirable peel value is the maximum value that does not causesignificant pain or damage to the skin upon removal.

Based on historical product performance of 3M SteriDrape™ and Ioban™products, typical dry peel testing does not accurately predictperformance characteristics of an incise drape. To better mimic realsurgical conditions, peel testing is performed after a relativelylengthy exposure to wet conditions. This type of testing has been foundto predict more accurately the performance of incise drapes duringsurgery.

CHG-containing adhesives were prepared using a variety of base PSAs andvehicles. The adhesive formulations are summarized in Tables 14a, 14b,and 14c. All the active formulation layers were coated at 4.6 mg/squarecentimeter.

TABLE 14a Compositions (wt. %) for formulations prepared with PSA-1. EX.PSA 1 Res-4 Res-4 GMO* GMIS-2 Glycerol CHG J1 74 10.7 — 10.7 — 3.6 1 J264 — 15 — 15 5 1 J3 64 — 15 15   — 5 1 *GMO = glycerol monooleate

TABLE 14b Compositions (wt. %) for formulations prepared with PSA-2. EX.PSA 2 Res-2 1,2-pentanediol Glycerol CHG J4 64 15 15 5 1

TABLE 14c Compositions (wt. %) for formulations prepared with PSA-3. EX.PSA 3 Res-3 Res-4 GMO* 1,2-pentanediol Glycerol MCM-2 CHG J5 59 20 — 20— — — 1 J6 54 22.5 — 22.5 — — — 1 J7 59 — 20 20 — — — 1 J8 64 — 15 — 155 — 1 J9 59 — 20 20 — — — 1 J10 54 — 22.5 22.5 — — — 1 J11 64 — 15 — — 515 1 *GMO = glycerol monooleate

Incise drape samples prepared using these adhesives and tested foradhesion performance by peel testing under wet conditions on the sideskin of a freshly euthanized pig. After the animal was euthanized, hairwas removed by shaving with a razor using only water. 70% IPA was thenused to clean the skin surface, and allowed to dry for 10 minutes. Drapesamples cut into 1.3 cm by 7.6 cm (0.5 inch by 3 inch) strips were thenapplied to the prepared skin such that the long axis of the drape samplewas oriented perpendicular to the spine. The drapes were then allowed tobuild adhesion for up to 5 minutes. After the dwell time, 10 cm by 10 cm(4 inch by 4 inch) gauze pieces soaked in 0.9% saline solution wereplaced over the drape samples. Extra saline was added to the gauze atten minutes intervals during the challenge period to keep it saturatedfor up to thirty minutes. After thirty minutes, the wet gauze wasremoved and samples were removed at a 90 degree angle, mechanically witha peel tester. The force of removal for each strip was recorded usingfour replicates. The results were compared to a commercially availableproducts; Ioban™ 2 Antimicrobial Incise Drape (“Drape 1”) available from3M Company, St. Paul, Minn. The averages and standard deviations arereported in Table 15.

These samples were also tested to further determine potentialperformance in real applications. For the Mock Surgery test, freshlyexcised porcine belly skin with underlying tissue intact (thicknessranging from 1.3 to 3.8 cm) (0.5 inch to 1.5 inch) was stretched taughtacross a board with nails. Hair was removed by dry clipping with anelectric razor (#50 blade). The skin was then cleaned with 70% IPA andallowed to dry for 15 minutes. Approximately 7.6 by 12.7 cm (3 inch by 5inch) drape samples were then applied to the skin, smoothed with gauze,and allowed to dwell and build adhesion for five minutes. After thedwell time, a new #10 scalpel blade was used to make a shallow 6 cmincision through the first few layers of skin using a single stroke ofthe blade. Then the blade was used to cut through the remaining tissueusing several strokes, but without further disturbing the initial cut.After the incision was made, gloved hands were used to pull and stretchthe incision in a semi-aggressive manner, ensuring that the drape/skininterface was contacted and rubbed by the gloves. This was continued fortwo minutes.

After two minutes, the incision edges were examined for areas where theadhesive drape had lifted away from the skin. Drape 1 remained adheredto the incision edge around the entire wound. Repeat testing of thisproduct using this method has shown that this drape reliably does notlift from the wound edge for more than 1 cm of the total incision edge(12 cm for a 6 cm incision). Therefore, the performance of thiscommercial drape under mock surgical conditions was used as theacceptance criteria for experimental drape performance. These resultsare also shown in Table 15.

TABLE 15 Peel Adhesion and Mock Surgery test results for Example Set J.Average Peel Force Standard Mock Surgery Wound EX. (g) n = 4 DeviationManipulation Test Drape 1 90 44 Pass J1 108 25 Pass J2 165 64 Pass J3143 29 Fail J4 38 2 Fail J5 72 25 Pass J6 97 14 Pass J7 134 39 Pass J844 10 Fail J9 119 35 Fail J10 102 15 Fail J11 39 11 Fail

The results show that several of the experimental drape samples hadaverage peel values greater than or equivalent to the Ioban™ incisedrape product. Based on the peel force data, one would expect that thesedrapes might perform equivalently to or better than such commercialincise drapes. The data also show observations from more rigorousperformance testing of the incise drape samples under conditionsmimicking surgery. In this test, some of the experimental drapes havinga high peel value and did not perform well under simulated surgicalconditions; thus, peel force alone cannot be used to predict adhesiveperformance of experimental incise drape constructions.

Data Set K. In some embodiments, the static dissipative properties of anadhesive article may be important for safe and proper handling andapplication. When the liner is removed from an adhesive, buildup ofstatic may occur. Such static can cause blocking to occur, and can makethe drape film attract to itself, making the product very difficult toapply. In some embodiments, the final construction might be required tomeet the specifications for minimizing the risk of spark generation perNFPA 99. The specifications require that the article pass a static decaytest where 5 kV of charge is dissipated in less than 0.5 seconds.

Static Dissipation Analysis. In some embodiments, the adhesive articlemust meet the specifications for minimizing the risk of spark generationper NFPA 99. The specifications require that the article pass a staticdecay test where 5 kV of charge is dissipated in less than 0.5 seconds(per industrial test method: IST 40.2-92 “Electrostatic Decay”).

Generally, adhesives by themselves are very hydrophobic and are notstatic dissipative. Usually an anti-static coating is put on the backingor liner to meet these specifications. In some embodiments, the adhesiveformulations can be prepared with vehicles that impart staticdissipative properties. The adhesive formulations described in Table 16acoated at 4.6 mg/square centimeter on Film-1 were tested for staticdissipation. The static dissipation results are shown in Table 16b.Formulations K1, K2, and K3 easily met the NFPA static dissipationrequirements.

TABLE 16a Compositions (wt. %) for Data Set K. Sorbitan EX. PSA-1 PSA-2Res-2 GMIS-2 Glycerol MCM-1 isostearate CHG K1 63 — 15 15 5 — — 2 K264.5 — 15 15 5 — — 0.5 K3 — 50 — 16 — 16 16 2 K4 — 50 — 24 — — 24 2 K5 —50 — 49 — — — 1

TABLE 16b Static dissipation results. Static decay time (sec.) EX. (+)(−) K1 0.34 0.32 K2 0.30 0.32 K3 0.07 0.07 K4 0.83 0.79 K5 1.24 1.18

Data Set L. Ex vivo samples were conducted using the compositionssummarized in Table 17. The standard sampling solution (“SSS”) was 75 mMphosphate-buffered water (0.04% KH₂PO₄, 1.01% Na₂HPO₄) containing 0.1%TRITON X-100 with 3% Polysorbate 80, 0.3% lecithin and 0.1% sodiumthiosulfate at pH 7.9±0.1. Various procedures were used to evaluateperformance with the results summarized in Tables 18a, 18b, and c.

TABLE 17 Compositions (% w/w) for Data Set L. Ex. Description PSA 1Res-2 GMIS-2 Glycerol CHG L1 Placebo 65 15 15 5 0 L2 Active 63 15 15 5 2

Procedure I: Analysis of drapes on porcine skin seeded with Serratiamarcescens. This experiment evaluated the effects of the active andplacebo drapes on the intact skin under the drapes after both were inplace for 4 hours. Recovery of the seeded bacteria from both the skinand drape were combined to determine the total antimicrobial effect.

1. Cut porcine abdominal skin into two sections and stretch out onboard. Remove hair by clipping and wipe away gross contamination.

2. Prepare a 10⁸ CFU/mL suspension of Serratia marcescens inPhosphate-Buffered Water (PBW) from an overnight growth plate. Dilute1:10 in PBW for 10⁷ CFU/mL working suspension. This is used to inoculatethe skin.

3. Saturate the sponge of a DURAPREP 8635 applicator (available from 3MCo.) with the Serratia working suspension. Start in the middle of thearea and wipe the sponge over the skin back and forth, moving out fromcenter in both directions. Re-saturate the same sponge and repeat withfresh suspension, changing direction by 90 degrees. Next use same spongebut do not re-saturate. Wipe from center out in a third direction. Letskin dry completely (30 minutes).4. Mark three areas in center of area to be draped by marking bottom ofa scrub ring with a sterile skin marker and touching to the skin. Removeliners from drape pieces and apply to skin. Smooth over top with sterilegauze. Mark areas on drape to correspond with the marked areas on theskin.5. Collect two baseline samples from inoculated areas around the drapesby the cup scrub method (ASTM E1874-09).6. Leave drapes in place for four hours at 35° C.7. After four hours on skin, remove each drape and place on a cleanliner. Scrub marked areas of skin underneath the drape using the cupscrub method (ASTM E1874-09). Serially dilute collected solutions;spread plate neat and diluted solutions on Trypticase Soy Agar (TSA)plates.8. Die cut three 25 mm samples from the marked areas on each drape.Transfer each separately to 20 mL Neutralizing Buffer (Difco) containing0.1% sodium thiosulfate. Sonicate for one minute and vortex vigorouslyfor two minutes. Serially dilute and spread plate all neat and dilutedsolutions on TSA plates.9. Incubate plates at 32° C. for three days.10. Count red colonies only (Serratia) on plates. Calculate bacteriarecovered per square centimeter. Add bacteria from correlating skin anddrape sites, and convert to log 10. Calculate the average of thetriplicate sites per drape.

TABLE 18a Log Recovery (n = 3) for drapes on seeded porcine skin(Serratia marcescens). Average Standard EX. Log Recovery deviation L14.1 0.2 L2 3.4 0.4

Procedure II: Incision Model on Seeded Porcine Skin (Serratiamarcescens). This model evaluates the active and placebo drapes in asimulated surgical procedure with shallow incisions through skin,retraction and manipulation. The use of seeded bacteria localizes thebacteria of interest to the skin surface initially and can bedifferentiated from normal flora.

1. Stretch and nail porcine abdominal skin to board. Clip hair and wipeaway gross contamination.

2. Prepare a 10⁸ CFU/mL suspension of Serratia marcescens inPhosphate-Buffered Water (PBW) from an overnight growth plate. Dilute1:10 in PBW for 10⁷ CFU/mL working suspension. This is used to inoculatethe skin.

3. Saturate the sponge of a DURAPREP 8635 applicator with the Serratiaworking suspension. Start in the middle of the area and wipe the spongeover the skin back and forth, moving out from center in both directions.Re-saturate the same sponge and repeat with fresh suspension, changingdirection by 90 degrees. Next use same sponge but do not re-saturate.Wipe from center out in a third direction. Let skin dry completely (30minutes).4. Collect baselines samples of bacteria. Place sterile metal templateonto skin (in area NOT covered by drapes). Prewet sterile swab in 1 mlSSS and rub swab on skin within template for 30 seconds. Return swab to1 ml tube, vortex 30 seconds, serially dilute and plate in TSA.5. Apply drape to skin, using sterile gauze to smoothly place drape andadhere it to the skin.6. Allow each drape to sit for five minutes.7. With a sterile scalpel blade (no. 10), make a six centimeter incisionthrough the drape. Cut through the fatty layer and into the muscle, butnot completely through the piece of skin to avoid contamination from theunderside of the skin section (approximately 1-2 cm deep).8. With sterile gloved fingers, manipulate the incision for one minute.Use the first two fingers on each hand to move around inside theincision and pull at the wound edges.9. Check for lifting of the drape along the incision edge.10. Retract incision approximately three centimeters with sterilestainless steel 5.5″ Weitlaner retractor.11. Moisten sterile gauze (two pieces of 12 ply gauze) with 25 mlsterile phosphate-buffered water (PBW) and place loosely over theretracted incision.12. Repeat process for a total of three incisions on each drape section.13. Cover skin with foil pan (loose) and incubate at 35° C. for a totalof four hours.14. After one hour, remove skin from incubator and remove gauze andretractors. Manipulate incision edges for fifteen seconds by rubbingwith gloved fingers around the incisions (on top of drape). Replaceretractors (keep retractors matched to their original incisions) andcover with new moistened gauze. Cover with foil pan and return to 35° C.incubator.15. Repeat step 14 after two total hours and again after three totalhours.16. After four hours, remove gauze and retractors. Evaluate eachincision for drape lift and visible fluid under the drapes.17. Collect bacteria along the edges of each incision. Prewet a sterileswab in a 1 ml tube of SSS and roll the swab twice around the inside ofthe incision. Break off swab into the tube of SSS and vortex for thirtyseconds. (“In incision” sample)18. Peel drape off of skin. Look for moisture on skin that may havemigrated under the drape.19. Collect bacteria from skin around incision edge. Prewet a sterileswab in a 1 ml tube of SSS and roll the swab once around the edge of theincision on the skin surface. Break off the swab into the tube of SSSand vortex for thirty seconds. (“Surrounding skin” sample)20. Serially dilute solutions with swabs and spread plate each ontoTrypticase Soy Agar (TSA) plates.21. Incubate plates for three days at 32° C.22. Calculate bacteria per mL (swab). Calculate the mean of theincisions per drape. Convert to log 10 CFU/swab.

TABLE 18b Log Recovery (n = 9) Incision Model on Seeded Porcine Skin(Serratia marcescens). “In incision” results “Surrounding skin” resultsAverage Standard Average Standard EX. Log Recovery deviation LogRecovery deviation L1 3.0 0.3 4.4 0.2 L2 2.2 0.4 3.7 0.2

There are differences between the placebo and active drapes with respectto the incision edges and on the skin immediately surrounding theincision. In both instances, there is lower log recovery from the activedrape (L2) than from the placebo drape (L1). The active drape issuperior to the placebo drape in the incision (95% confidence).

Procedure III: Incision Model on Porcine Skin (Normal Flora). This modelevaluates the active and placebo drapes in a simulated surgicalprocedure with shallow incisions through skin, retraction andmanipulation. Procedure III was identical to Procedure II, except thatSteps 2 and 3 were not performed. Also, a modified Standard SamplingSolution was prepared with Tamol (“SST”) containing 75 mMphosphate-buffered water (0.04% KH₂PO₄, 1.01% Na₂HPO₄) containing 0.1%TRITON X-100 with 1% Polysorbate 80, 0.3% lecithin and 1% Tamol with pH7.9±0.1 was used.

TABLE 18c Log Recovery (n = 6) Incision Model on Porcine Skin (NormalFlora). “In incision” “Surrounding skin” Average Standard AverageStandard EX. Log Recovery deviation Log Recovery deviation L1 2.4 0.54.0 0.8 L2 1.3 0.4 3.0 0.5

There are differences between the placebo and active drapes with respectto the incision edges and on the skin immediately surrounding theincision. The 1 log difference in the incision is statisticallysignificant with a p-value of <0.001. There is a 1 log difference on theskin surface also, however it was not statistically significant (p-valueof 0.17).

Various modifications and alterations of this invention will becomeapparent to those skilled in the art without departing from the scopeand spirit of this invention.

What is claimed is:
 1. A composition comprising chlorhexidine gluconatesolubilized in a hydrophobic vehicle having a hydrophilic-lipophilicbalance of no greater than 10 as determined using the HLB Method,wherein the hydrophobic vehicle comprises two proximate hydrogen-bondinggroups, wherein at least one of the hydrogen-bonding groups is ahydrogen donor, wherein the composition comprises no greater than 2parts by weight hydrophilic vehicle per 1 part by weight chlorhexidinegluconate, and wherein the hydrophobic vehicle comprises an etherfunctional group.
 2. The composition of claim 1, wherein the hydrophobicvehicle is dipropylene glycol.
 3. The composition of claim 1, whereinthe hydrophobic vehicle is a glyceryl monoalkyl ether.
 4. Thecomposition of claim 3, wherein the glyceryl monoalkyl ether isethylhexylglycerin.
 5. The composition of claim 1, wherein thecomposition comprises no greater than 1 part by weight hydrophilicvehicle per 1 part by weight chlorhexidine gluconate.
 6. The compositionof claim 1, wherein the composition comprises no greater than 0.5 partby weight hydrophilic vehicle per 1 part by weight chlorhexidinegluconate.
 7. The composition of claim 1, wherein the compositioncomprises no greater than 0.1 parts by weight hydrophilic vehicle per 1part by weight chlorhexidine gluconate.
 8. The composition of claim 1,wherein the composition comprises no greater than 1 part by weight waterper 1 part by weight chlorhexidine gluconate.
 9. The compositionaccording to claim 5, wherein the composition comprises no greater than0.1 parts by weight water per 1 part by weight chlorhexidine gluconate.10. The composition according to claim 1, further comprising a resinsystem comprising a polymer.
 11. The composition of claim 10, whereinthe resin system comprises a hydrophobic phase, wherein the hydrophobicvehicle plasticizes the hydrophobic phase.
 12. The composition of claim10, wherein the polymer comprises an acrylate polymer.
 13. Thecomposition of claim 10, wherein the polymer comprises a block copolymerpolymer.
 14. The composition according to claim 11, wherein the resinsystem is a pressure sensitive adhesive.
 15. An article comprising asubstrate and the composition according to claim 1 is bonded to at leasta portion of a surface of the substrate.
 16. The article according toclaim 15, wherein the article is a medical article.